Apparatus for producing microspheres

ABSTRACT

Apparatus for producing microspheres including a vertically mounted sol-gel feed tube having a lower microsphere formation needle immersed in an alcohol drying column, variable pump means for feeding sol-gel at a predetermined rate into the upper end of the feed tube, and drive means for vibrating the feed tube in a generally horizontal direction at a predetermined amplitude and frequency to produce microspheres from the formation needle of a uniform and predetermined size. An electromagnetic transducer drive for vibrating the feed tube is used in one illustrative embodiment of the invention, and an electric motor offset drive is used in another illustrative embodiment thereof. A feed tube having multiple microsphere formation needles at its lower end can be used for producing microspheres in quantity.

United States Patent 1 Lysher [451 Apr. 24, 1973 APPARATUS FOR PRODUCING Primary Examiner-J. Spencer Overholser MICROSPHERES Assistant ExaminerMichael 0. Sutton 75 Inventor: Wayne M. Lysher, Richland, Wash. ff Donald Ryer and [73] Assignee: McDonnell Douglas Corporation, I

Santa Monica, Calif. [57] v ABSTRACT [22] Filed: Dec, 17, 1970 Apparatus for producing microspheres including a vertically mounted sol-gel feed tube having a lower [21] Appl' 98975 microsphere formation needle immersed in an alcohol drying column, variable pump means for feeding sol- 52 U.S. C1 ..425/210, 264/9 gel 318 predetenfiined rate inwfhe PPP end of the 51 Int. Cl. ..B22d 23/08 F tube and W mean? f the feed F [58] Field of Search ..18/2.4, 2.7; 264/9; genrauy horzomal drecnon prefietermmed 425/6 10 amplitude and frequency to produce mlcrospheres from the formation needle of a uniform and predetermined size. An electromagnetic transducer drive for [56] cued vibrating the feed tube is used in one illustrative em- UNITED STATES PATENTS bodiment of the invention, and an electric motor off- 1 set drive is used in another illustrative embodlment 3,373,232 3/1968 Wise et al ..264/9 the eofi A feed tube having multiple microsphere for- 3,123,855 3/1964 Fischer et al..... ..18/2.7 mation dl at it lower end can be used for 3,340,567 9/1967 Flack et al ..18/2.7 producing microspheres in quantity 2,574,357 ll/l95l Stammer 'et al.. .ll8/2.4 X 2,510,574 6/1950 2 Claims, 5 Drawing Figures Greenhalgh ..18/2.7 X

Mario/1216 95;

APPARATUS FOR PRODUCING MICROSPHERES BACKGROUND OF THE INVENTION My present invention relates generally to radioisotope microspheres. More particularly, the invention relates to a novel process and associated apparatus for rapidly and efficiently producing uniformly sized microspheres.

Radioisotope microspheres are normally formed by the sol-gel process which is a wet-chemistry technique. A starting (nitrate) compound is suitably dissolved, the metal hydroxide precipitateis washed, andcrystallite (oxide) growth is controlled and concentrated by heat and evaporation. The resulting sol-gel ofa suitable consistency or viscosity is formed into microspheres which are then calcined in a furnace at approximately l,500 C to achieve near-theoretical density. The sol-gel process has proven advantages including high density microsphere formation capability, reasonable economy, wide reproducible size range, and minimal airborne scattering or loss of radioactive particles.

In the conventional process of forming sol-gel microspheres, the sol-gel is fed at a flow rate according to its consistency or viscosity alongwith a flow of alcohol. The sol-gel is contained in an ordinary syringe mounted on an infusion pump which can be varied to drive the syringe plunger at a desired rate. The sol-gel output from the syringe is fed through a flexible tubing into a squared tip hypodermic needle, the end of the tubing being connected to the upper end of the needle by a suitably tapered connector. The tapered connector is installed in a coupling collar at the top of a relatively long microsphere formation nozzle so that the hypodermic needle is concentrically mounted and extends down within the tubular nozzle. The length of the needle is, for example, about 2 inches long and the nozzle is about 6 inches long, with the lower 1 inch of the nozzle immersed in a microsphere drying alcohol column.

The coupling collar has a laterally connecting passageway opening adjacent to the tapered wall of the tapered connector. Alcohol is fed in the passageway and flows around the tapered wall of the tapered connector and down the outside of its connected needle. The alcohol flows pass the end of the hypodermic needle and generally keeps the surrounding tubular nozzle filled with its flow. Microsphere formation is accomplished by the alcohol flow acting on the sol-gel emitted at the end of the needle. The alcohol flow inevitably fluctuates, however, and produces a considerable effect on the formation of the microspheres. Size variation is a major result and this causes a high rejection rate of unsuitably sized microspheres. Provision of a proper alcohol feed with the sol-gel feed precludes the satisfactory use of more than one needle within a microsphere formation nozzle. Thus, production of microspheres in quantity is infeasible with this equipment. The inherent static operating conditions of the equipment also account for a certain amount of the variations in sol-gel viscosity and needle plugging by the sol-gel. I

SUMMARY OF THE INVENTION Briefly, and in general terms, my invention is preferably accomplished by providing apparatus for producing microspheres including a vertically mounted sol-gel feed tube having at least one microsphere formation needle suitably coupled to its lower end, an infusion pump having a variable drive for feeding sol-gel from its driven syringe at a predetermined rate into the upper end of the feed tube, a container providing an alcohol column in which the lower end of the feed tube is immersed, drive means for vibrating the feed tube such that the lower end of the formation needle is generally displaced horizontally at a predetermined amplitude and frequency to produce microspheres from the needle immersed in the alcohol'column of a uniform and predetermined size, and a circulating pump for providing a'flow of alcohol up through the container at a predetermined flow rate for suspending a quantity of drying microspheres in the alcohol column.

Uniform microspheres of a predetermined size can be produced with a fixed sol-gel feed rate according to the size of the formation needle used and its vibrated amplitude and frequency. The size of the formation needle and its vibration amplitude normally need not be changed for different production runs so that microsphere size can be essentially a function of vibration frequency. An electromagnetic transducer (Low Frequency Audio Driver) for vibrating the feed tube is used in one illustrative embodiment of this invention, and an electric motor offset (crank) drive is used in another illustrative embodiment thereof. A feed tube having multiple microsphere formation needles at its lower end can be used to produce microspheres in quantity by vibrating the needles perpendicularly to the sol-gel feed direction. The number of needles used is limited only by the feed tube size.

BRIEF DESCRIPTION OF THE DRAWINGS My invention will be more fully understood, and other features and advantages thereof will become apparent, from the following-description of two exemplary embodiments of the invention. The description is to be taken in conjunction with the accompanying drawings, in which:

FIG. 1 is a diagrammatic representation of an illustrative embodiment of this invention wherein an electromagnetic transducer drive is used to actuate a solgel feed tube to produce microspheres in accordance with my invention;

FIG. 2 is a fragmentary and enlarged sectional view of the sol-gel feed tube used in the embodiment of FIG.

FIG. 3 is a generally perspective view of another illustrative embodiment of this invention wherein an electric motor offset drive is utilized to actuate a pivotally mounted sol-gel feed tube;

FIG. 4 is a fragmentary cross sectional view of the pivotally mounted sol-gel feed tube as taken along the line 44 indicated in FIG. 3; and

FIG. 5 is another cross sectional view of the pivotally mounted sol-gel feed tube as taken along the line 5-5 indicated in FIG. 3.

DESCRIPTION OF THE PRESENT EMBODIMENTS FIG. 1 is a diagrammatic representation of an illus trative embodiment of my invention, This embodiment utilizes an electromagnetic transducer drive and can be appropriately designated as the electromagnetic transducer microsphere production system 10. The system includes a function generator 12 having an alternating current output, a power amplifier 14 for amplifying thegenerator output signaL'an electromagnetic transducer 16 which is energized by the amplifier output signal t0-produce a mechanical output, a vertical solgel feed tube 18 which is driven (horizontally vibrated) by the transducer output to produce microspheres 20 therefrom, a container 22 providing an alcohol column 24 for receiving and drying the microspheres, and a pump 25 for'circulating the alcohol at a proper flow rate for suspension of a quantity of the formed microspheres therein. An alcohol reservoir 26 and a flow meter 27 are respectively located before and after the circulating pump 25, as shown.

The function generator 12 can be, for example, a Model 202A Low Frequency Function Generator manufactured by the Hewlett Packard Company of Palo Alto, California for providing a sine wave output signal which can be adjusted in amplitude and varied in frequency. The output signal of the function generator 12 can be varied from 50 to 150 c.p.s., for example. The power amplifier 14 is conventional and can provide output power of 75 to 100 watts audio for energizing the electromagnetic transducer 16. The elec-. tromagnetic transducer 16 can be essentially an ordinary loud-speaker wherein the output signal of the power amplifier 14 is applied to speaker audio coil 28. The coil 28 is wound on and bonded to a tubular hub 30 which is attached at its right end to the periphery of a central circular opening in diaphragm 32. The radially outer periphery of the diaphragm 32 is supported by the right end of transducer casing 34 through a flexible connection 36. The ends of the coil 28 are connected to respective connectors 38 suitably mounted to the casing 34, and the output of the power amplifier 14 is connected to the connectors as shown in FIG. 1.

The tubular hub 30 is supported so that it is concentrically positioned about the cylindrical end of the permanent field magnet core 40. The right end of the hub 30 is closed normally by disc 42 which has been modified to be centrally affixed to the left end ofa connecting rod 44. The right end of the connecting rod 44 is suitably affixed to clamp means 46 which directly mounts vertical sol-gel feed tube 18. The feed tube 18 includes an upper portion 48 into which sol-gel is normally fed, and a lower portion 50 which is conically tapered at its lower end to join with a hollow microsphere forming needle 52. The lower portion 50 of the feed tube 18'is immersed in the alcohol column 24 which is held in the container 22. The alcohol is circulated by pump 25 through a circulating passageway 54 at a microsphere suspension flow rate which is determined by the size of the drying column 24 and the quantity of formed microspheres 20 held in suspension. The alcohol needs to be at room temperature only, and a flow rate must be maintained to allow suspension of the formed microspheres until an adequate drying time.

has elapsed (about 30 minutes, for example). Some trial and error is necessarily involved in establishing the I proper alcohol flow rate, of course.

FIG. 2 is a fragmentary and enlarged sectional view of the sol-gel feed tube 18 portion of the system- 10 shown in FIG. 1. An infusion pump (with a variable feed rate drive) and syringe 56 designed to accom- I modate an ordinary syringe with sufficient sol-gel for a prolonged run time has the syringe output coupled by flexible tubing,5 8 tothe upper end offeed tube 18. The infusion pump and syringe 56 is, for example, a Model 975 Compactlnfusion Pump manufactured by the Harvard Apparatus Company of Dover, Massachusetts mounting an ordinary syringe thereon in its bracket so that the pump drive engages the syringe plunger. The feed tube 18 can have an upper portion 48 inner diameter of approximately one-fourth inch and a lower portion 50 tapered length of about three-eighths inch, for example; The microsphere forming needle 52 can be a No. 22 hypodermic needle having a one thirty-second inch outer diameter, a 12 to 15 mils inner diameter or bore, and a length of about one-half inch with a squared tip. The needle 52 length must not be too long (and should be less than I inch in length) to be adequately rigid in order to avoid any tendency towards higher harmonic frequency motions. The particular models of equipment and types of materials, and specific rates and dimensions noted above and elsewhere herein are, of course, merely given by way of example only and are not to be considered as limiting on this invention in any manner.

In operation, the function generator 12 (FIG. 1) is adjusted to provide an output signal of, for example, a frequency of 90 c.p.s. and an amplitude which produces a horizontal or lateral displacement of the needle 52 of approximately one-sixteenth inch total. The infusion pump (and syringe) 56 (FIG. 2) is adjusted to provide a feed rate of, for example, 46 c.c. per minute of samarium hydroxide [Sm(OH) sol-gel. Of course, the sol-gel consistency or viscosity determines the flow rate to be provided for microsphere formation and the size is determined by needle size, displacement amplitude and frequency. It is not always possible to obtain a sol-gel solution of the same consistency; therefore, some trial and error is employed in establishing the proper feed rate for uniform microsphere formation. The sol-gel used is an aqueous colloidal solution or system wherein the solid material mixed and suspended therein is samarium hydroxide having a molar constituent varying from I to 4, for example. Other solid materials that have been used in the sol-gel solution to form microspheres include neodymia (Nd o promethia (Pm O and most of the rare earths.

FIG. 3 is a generally perspective view of another il-- lustrative embodiment of this invention. This embodiment utilizes an electric motor offset drive and can be appropriately designated as the electric motor microsphere production system 60. The system 60 includes a variable speed motor 62, a flywheel 64 suitably coupled centrally to the drive shaft 66 of the motor, a normally vertical sol-gel feed tube 68 rotatably mounted directly on an adjustable pivot point 70, and a connecting rod 72 attached at its left end to an off-center crankpin 74 on the flywheel and at its right end to the web 76 of a U-shaped bracket 78 rotatably attached to its arms 80 to an upper connection point 82 directly on the feed tube. The motor 62 can be either an alternating or direct current motor variable in speed from 3,000 to 6,000 r.p.m., for example.

The adjustable pivot point can be set on the feed tube 68 by moving it in the clamp 84 and then tightening the clamp at'a desired pivot point along the length of the feed tube. The clamp 84 has diametrically extending pivot pins 86 which are rotatably mounted and secured to respective arms 88 of U-shaped bracket 90. The web 92 of the bracket 90 is connected by a mounting rod 94 to fixed structure as indicated. A suitable sol-gel solution is fed to the upper end 96 of the feed tube 68 by an infusion pump and its syringe (not shown) in the same manner as that shown in FIG. 2. The lower end 98 of the feed tube 68 is, of course, also suitably immersed ina circulated alcohol drying column (not shown) in the same manneras that illustrated in FIG. 1. While four hollow, squared end, microsphere forming needles 100 are actually joined to and extend from the lower end 98 of the feed tube 68 in this particular embodiment of the invention, the number of needles that can be used is limited only by the size of the feed tube.

FIG. 4 is a fragmentary cross sectional view of the pivotally mounted sol-gel feed tube 68, as taken along the line 4-4 indicated in FIG. 3. In this cross sectional view, the connection point 82 is seen to be a diametrical line which is perpendicular to the arms 80 of the U- shaped bracket 78. The arms 80 are rotatably mounted and secured to respective attachment pins 102 which extend diametrically from a clamp 104. The clamp 104 is, of course, fastened to the feed tube 68 at the desired connection point 82 along the length thereof. The relative positions of the pivot and connection points 70 and 82 are chosen to provide a predetermined horizontal or lateral displacement. of the ends of the needles 100 as indicated by the arrow 106 shown in FlG. 3. The actual movement of the ends of the needles 100 is, of course, along an are which is centered on the pivot point 70. The vertical displacement, as contrasted with the horizontal displacement, of the ends of the needles 100 is, however, virtually imperceptible over the normal displacement range of travel (of the order of one-sixteenth inch) involved.

FIG. 5 is another cross sectional view of the pivotally mounted sol-gel feed tube 68, as taken along the line 5-5 indicated in FIG. 3. The lower end 98 (FIG. 3) of the feed tube 68 is generally flattened and tapered inwardly towards the needles 100. The upper ends of the needles are thus joined to a closed, narrow width, rectangular end of the feed tube 68. In this instance, the needles 100 are arranged in a row as shown in FIG. 5. While the needles 100 are vibrated laterally in the direction of the solid line arrow 106, they can also be suitably vibrated laterally in the direction of the broken line arrow 108 which is perpendicular to the solid line arrow. This can be easily accomplished by loosening the clamps 84 and 104 and rotating the feed tube 68 (FIG. 3) on its axis 90 degrees, and then tightening the clamps again. The needles 100 can, of course, be arranged in patterns or configurations other than a straight row as illustrated in FIGS. 3 and 5. Further, the needles 100 can, if desired, have different diameter bores to produce different sized microspheres simultaneously during a production run.

A fairly wide range of microsphere sizes can be produced with needles of a given bore diameter by varying their vibration frequency. Other ranges can be similarly obtained by using needles of larger or smaller bore diameters, of course. lt should also be noted that the needles 100 (FIGS. 3 and 5) must be adequately spaced apart so that there is no interference in microsphere formation between adjacent needles. Using No. 22 needles, for example, the needles 100 are preferably spaced at approximately one-eighth inch intervals.

The operation with multiple feed needles 100 is similar to that (FIGS. 1 and 2) with a single feed needle 52, in that uniform microspheres are formed by a breaking actiontas the feed needles vibrate perpendicularly to the direction of sol-gel flow. The invention can be built as a small scale, single needle, unit or as a large scale, multiple needle, unit which is feasible for production of microspheres in quantity. Alcohol feed used conventionally with sol-gel feed is eliminated in this invention, such that the usual fluctuating alcohol feed acting on the sol-gel feed is not present to affect the resulting microsphere size. The consequential variation in microsphere size is greatly reduced to a very small rejection rate. lllustratively, in a worst embodiment" case, the yield from a 50 c.c. syringe supply of sol-gel exceeded 80 percent in the 600 micron size range for a permissible variation of i 50 microns with a pneumatically vibrated seven-needle embodiment of the multiple needle version of this invention. This pneumatically or air-actuated vibrator embodiment of the invention has not been shown herein because of the presently better performance and more precise control available from the electromagnetic transducer and electric motor microsphere production embodiments.

The apparatus and process described above are unique in their concept to produce microspheres without the need for complicated control of simultaneous alcohol and sol-gel feeds required in the conventional apparatus and process. Microsphere production by (lateral) vibration eliminates the need for a simultaneous alcohol flow and assures a more homogeneous solution prior to microsphere formation, thereby greatly reducing any needle plugging due to variations in sol-gel consistency or viscosity; and by this very action produces uniformly sized spheres. The results include apparatus having a considerable simplification over the equipment conventionally required and vastly greater reliability in forming very accurately sized microspheres. The man-hours required in monitoring sol-gel microspheres productionruns have been very significantly reduced with this invention.

While certain exemplary embodiments of this invention have been described above and shown in the accompanying drawings, it is to be understood that such embodiments are merely illustrative of, and not restrictive on, the broad invention and that I do not desire to be limited in my invention to the details of construction or arrangements shown and described, for obvious modifications may occur to persons skilled in the art.

I claim:

, 1. Apparatus for producing high yields of microspheres of a very uniform and predetermined size, said apparatus comprising:

a sol-gel feed tube including a lower microsphere formation nozzle, said nozzle comprising at least one hollow straight needle generally aligned longitudinally with said feed tube and having a predetermined, uniform, hollow cross sectional open area and a bottom, squared tip, opening for providing a longitudinal flow of sol-gel therefrom, and said needle being relatively short and adequately rigid to avoid any tendency towards harmonic frequency motions;

means for feeding Sol-gel at a predetermined rate into the upper end of said feed tube;

a container including a formed microsphere drying liquid column therein;

an electromagnetic transducer means including a drive device, said transducer means being electrically energizable to actuate said drive device;

a function generator means for providing a sine wave electrical output signal adapted to energize said transducer means and reciprocally actuate said drive device;

connecting means including a rod connected on one end to said drive device and adapted to mount said feed tube directly on the other end, said feed tube being freely supported solely by said drive device through said connecting means in a generally vertical position with its lower portion immersed in said liquid column and can be reciprocally actuated independently by said drive device when said transducer means is energized by said generator means, said needle being thereby laterally reciprocated at a predetermined amplitude and frequency whereby the lower end of said needle is reciprocally displaced over a predetermined travel in a generally horizontal direction, substantially perpendicular to said flow of sol-gel, to produce formed microspheres therefrom of a predetermined size according to said hollow cross sectional open area of said needle and its horizontal recipro-.

cation amplitude and frequency, and said generator means can be adjusted to vary the frequency only of said electrical output signal and hence similarly of said needle whereby microsphere size 7 is essentially a function of said needle reciprocation'frequency alone and said needle of the same predetermined hollow cross sectional open area can be used without altering its reciprocation amplitude for production runs of different sizes of microspheres; and

means for suspending a quantity of said formed microspheres in said liquid column, said suspending means including an upward liquid flow produced by pump means circulating the liquid in said column at a predetermined flow rate to suspend the quantity of said formed microspheres therein. V

2. Apparatus for producing high yields of microspheres of a very uniform and predetermined size, said apparatus comprising:

a sol-gel feed tube including a lower microsphere forliquid column therein; means for mounting Said feed tube directly on a longitudinal pivot point in a normally vertical position with its lower portion immersed in said liquid column, said feed tube being freely rotatably and solely supported on said pivot point;

a variable speed electric motor including an output shaft, said motor being electrically energizable to rotate said output shaft;

offset drive means including a flywheel centrally mounted to said output shaft and an off-center crankpin affixed to said flywheel;

connecting means including a rod connected on one end of said crankpin and on the other end to a connection point directly on said feed tube above its pivot point to oscillate said feed tube independently on said pivot point through said drive means when said motor is energized, said needle being thereby oscillated at a predetermined amplitude and frequency whereby the lower end of said needle is reciprocally displaced over a predetermined travel in a generally horizontal direction, substantially perpendicular to said flow of sol-gel,- with negligible travel in a generally vertical direction to produce formed microspheres therefrom of a predetermined size according to said hollow cross sectional open area of said needle and its horizontal reciprocation amplitude and frequency; and

means for suspending a quantity of said formed microspheres in said liquid column, said suspending means including an upward liquid flow produced by pump means circulating the liquid in said column at a predetermined rate to suspend the quantity of said formed microspheres therein. 

2. Apparatus for producing high yields of microspheres of a very uniform and predetermined size, said apparatus comprising: a sol-gel feed tube including a lower microsphere Formation nozzle, said nozzle comprising at least one hollow straight needle generally aligned longitudinally with said feed tube and having a predetermined, uniform, hollow cross sectional open area and a bottom, squared tip, opening for providing a longitudinal flow of sol-gel therefrom, and said needle being relatively short and adequately rigid to avoid any tendency towards harmonic frequency motions; means for feeding sol-gel at a predetermined rate into the upper end of said feed tube; a container including a formed microsphere drying liquid column therein; means for mounting said feed tube directly on a longitudinal pivot point in a normally vertical position with its lower portion immersed in said liquid column, said feed tube being freely rotatably and solely supported on said pivot point; a variable speed electric motor including an output shaft, said motor being electrically energizable to rotate said output shaft; offset drive means including a flywheel centrally mounted to said output shaft and an off-center crankpin affixed to said flywheel; connecting means including a rod connected on one end of said crankpin and on the other end to a connection point directly on said feed tube above its pivot point to oscillate said feed tube independently on said pivot point through said drive means when said motor is energized, said needle being thereby oscillated at a predetermined amplitude and frequency whereby the lower end of said needle is reciprocally displaced over a predetermined travel in a generally horizontal direction, substantially perpendicular to said flow of sol-gel, with negligible travel in a generally vertical direction to produce formed microspheres therefrom of a predetermined size according to said hollow cross sectional open area of said needle and its horizontal reciprocation amplitude and frequency; and means for suspending a quantity of said formed microspheres in said liquid column, said suspending means including an upward liquid flow produced by pump means circulating the liquid in said column at a predetermined rate to suspend the quantity of said formed microspheres therein. 